The Phelan Lab
@ CU Anschutz Medical Campus
CULTUROMICS OF MICROBIOMES
In this project, we recapitulate native microbiomes in vitro.
Premise: In microbiome research, we are quickly learning which microbes are present in a community, but have little knowledge about how they interact with each other and their environment. Part of the challenge of studying the chemistry of microbiome communities is that the metabolites produced are at low concentration. Therefore, in vitro model systems are an enticing option for studying complex chemistry due to their higher throughput, flexibility, scalability, and ability to simplify the system for high resolution molecular analyses.
Ongoing work: We're developing two culturomics systems. One system recapitulates the chronic lung infections affecting people with cystic fibrosis. This system is used to investigate how microbes interact in mock and ex vivo microbiome communities. The second system uses a soil-based medium to induce secondary metabolite production by Actinobacteria. This system is used to investigate soil microbiomes and their response to environmental contaminants.
POLYPHARMACY AND MICROBIAL VIRULENCE
In this project, we evaluate how multidrug therapy influences pathogen virulence.
Premise: In the treatment of many chronic diseases, patients are treated with a wide variety of drugs to treat the underlying disease, co-morbidities, and complications. Unfortunately, our understanding of the impact of polypharmacy on the microbiome is limited. Additionally, many human targeted treatments have been shown to act as antibiotics and sub-inhibitory antibiotics have been implicated in increasing microbial virulence and biofilm formation. Therefore, it is important to elucidate the effect of polypharmacy on microbial virulence.
Ongoing work: Our current focus is on the impact of antibiotics on the quorum sensing pathways of the pathogen Pseudomonas aeruginosa. P. aeruginosa an ESKAPE pathogen with a well-characterized metabolome. We are expanding our focus to investigate the effect of polypharmacy of mock and ex vivo CF pulmonary microbiome communities.
LIPID DYSREGULATION IN CHRONIC LUNG DISEASES
In this project, we investigate how host lipid dysregulation affects the microbiome.
Premise: Chronic lung diseases are one of the leading causes of death in developed countries. One of the commonalities between all chronic lung diseases is dysregulation of lipid production, including ceramides and proinflammatory oxylipins. However, we know very little about how this dysregulation affects microbial communities and pathogens.
Ongoing work: Loss of the function of the cystic fibrosis transmembrane conductance regulator (CFTR) causes lipid dysregulation in the CF airway. We're investigating how new therapeutics such as CFTR modulators influence CF airway lipid profiles and microbial virulence factor production.